Glycine-enhanced inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase-I by EDTA: a full account of the reported inhibition by commercial preparations of acidic fibroblast growth factor (FGF-1).
The earlier reported inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase I (EC 3.1.6.9/EC 3.1.4.1; NPP/PDE) by culture-grade acidic fibroblast growth factor (FGF-1) correlates with a low-Mr contaminant. 1H-NMR analyses revealed EDTA in the total-volume fractions of a gel-filtration experiment, where all the inhibitory activity of the FGF-1 preparation was recovered. NPP/PDE inhibition by EDTA (and by unfractionated FGF-1 or the EDTA-containing fractions) was time-dependent, blocked by the substrate p-nitrophenyl-dTMP, and strongly enhanced by glycine. The use of glycine buffers in earlier work was critical to the apparent inhibition by FGF-1. The results point to a conformational change favored by glycine that may be relevant to the biological role of NPP/PDE.
López-Gómez
J
J
Unidad de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain.
Costas
M J
MJ
Meireles Ribeiro
J
J
Fernández
A
A
Romero
A
A
Avalos
M
M
Cameselle
J C
JC
D000818:Animals; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D043264:Phosphodiesterase I; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors*; D051381:Rats
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D016220:Fibroblast Growth Factor 1; D004492:Edetic Acid; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; D011755:Pyrophosphatases; C021899:nucleotide pyrophosphatase; D005998:Glycine